Li Tian-le, Fu Mao-Long, Wang Li-Hong, Wang Jian-Long, Liu Ying-Wu, Huang Lei
Heart Center, Tianjin Third Central Hospital Tianjin, China.
Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases Tianjin, China.
Eur Cardiol. 2025 Apr 1;20:e07. doi: 10.15420/ecr.2024.44. eCollection 2025.
This study investigates the causal relationships between 731 immune cell traits and aortic dissection (AD) using Mendelian randomisation (MR). By identifying specific immune cell phenotypes contributing to AD, we explore their clinical implications for risk stratification and therapeutic interventions.
A bivariate MR framework analysed the causal dynamics between immune cell attributes and AD, using genetic variants as instrumental variables. Summary statistics from a genome-wide association study for 731 immune phenotypes were obtained. Univariable MR analysis was conducted using the inverse-variance weighted method supplemented by sensitivity analyses. Horizontal pleiotropy was assessed using MR-Egger and MR pleiotropy residual sum and outlier. Significant cis-expression quantitative trait loci (eQTL) were identified via the Genotype-Tissue Expression (GTEx) database, followed by tissue-specific expression and pathway analyses.
Four immunophenotypes exhibited positive causal effects on AD, while one showed a negative effect. Pathogenic traits included the median fluorescence intensity of CD19 on transitional B cells, immunoglobulin D CD38dim B cells, CD3 on CD39 CD4 Treg cells, and CD3 on CD39 activated Treg cells. The protective trait was the absolute count of CD86 myeloid dendritic cells. Sensitivity analyses validated these associations. Pathway enrichment analysis highlighted significant arterial enrichments and key biological processes, identifying SLAMF6 and CD28 as key genes.
This study suggests potential causal roles for specific immune cell traits in AD pathogenesis, although these findings should be interpreted with caution due to study limitations. The identified immune cell types and associated eQTL genes offer promising targets for clinical risk stratification and therapeutic interventions. Future research should focus on translating these findings into practical strategies for patient care.
本研究采用孟德尔随机化（MR）方法探究731种免疫细胞特征与主动脉夹层（AD）之间的因果关系。通过确定导致AD的特定免疫细胞表型，我们探讨它们在风险分层和治疗干预方面的临床意义。
采用双变量MR框架，以基因变异作为工具变量，分析免疫细胞属性与AD之间的因果动态关系。获得了731种免疫表型的全基因组关联研究的汇总统计数据。使用逆方差加权法进行单变量MR分析，并辅以敏感性分析。使用MR-Egger以及MR多效性残差和离群值评估水平多效性。通过基因型-组织表达（GTEx）数据库鉴定显著的顺式表达数量性状位点（eQTL），随后进行组织特异性表达和通路分析。
四种免疫表型对AD表现出正向因果效应，而一种表现出负向效应。致病特征包括过渡性B细胞上CD19的中位荧光强度、免疫球蛋白D CD38dim B细胞、CD39 CD4调节性T细胞（Treg）上的CD3以及CD39活化Treg细胞上的CD3。保护性特征是CD86髓样树突状细胞的绝对计数。敏感性分析验证了这些关联。通路富集分析突出了显著的动脉富集和关键生物学过程，确定信号淋巴细胞激活分子家族6（SLAMF6）和CD28为关键基因。
本研究表明特定免疫细胞特征在AD发病机制中可能具有因果作用，尽管由于研究局限性，这些发现应谨慎解读。所确定的免疫细胞类型和相关的eQTL基因可为临床风险分层和治疗干预提供有前景的靶点。未来的研究应专注于将这些发现转化为患者护理的实用策略。
